Abstract
Background: In this study, novel ortho-hydroxy N-acyl hydrazone moiety including compounds (3a-l) were designed, based on procaspase activating compound (PAC-1) which is a small molecule known with antitumor activity. The antitumor activity was evaluated on A549 (human lung cancer cell line) and CCD 19Lu (human lung normal cell line).
Methods: Twelve N'-arylidene-2-[4-(methylsulfonyl)piperazin-1-yl]acetohydrazide derivatives (3a-l) were synthesized starting from ethyl 1-piperazinylacetate. All compounds were tested using MTT method and Xcelligence-Real time cell analysis system (RTCA DP) to determine their antitumor activity.
Results: Some physicochemical properties of four active compounds were also predicted using MolSoft, PreADMET and PROTOX software. Four of them, 3h, 3j, 3k and 3l bearing 3-hydroxy, 4-dimethylamino, 2,6-dichloro and 3,4-dichloro substituents in order exhibited selective cytotoxicity.
Conclusion: Eligible values were obtained in the specified ranges as to be an oral/intravenous drug considering the physicochemical calculations.
Keywords: Lung cancer, hydrazone, Procaspase Activating Compound (PAC-1), real-time cell analysis, physicochemical properties, antitumor activity.
Graphical Abstract
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